[unreadable] Diffuse optical imaging (DOI) alone offers the possibility of simultaneously and non-invasively measuring neuronal and vascular signals in the brain cortex. However, while the optical measurement of hemodynamic signals is well established, optical measurement of neuronal activation (the fast signal) is just emerging and requires further optimization and validation. Our hypothesis is that the current limitations of optical techniques for noninvasive measurement of the neuronal fast signal are not determined by intrinsic features of the optical effect of neuron activation, but rather are the result of a less-than-optimal experimental approach. We will increase the robustness of our measure of the fast signal by improving the instrumentation, the stimulation protocols, and the signal processing, and then assess its efficiency, reproducibility, and reliability with noninvasive measurement in animals (rats and monkeys) and adult human subjects (Aim 1). Once the optical technique is optimized: (1) We will test the hypothesis of a scattering origin of the fast signal (Aim 2) by determining its spatial and spectral features. (2) We will validate the fast optical signal as a measure of neuronal activity by correlating the fast signal with invasive electrophysiology measures in rats and EEG/MEG measures in humans (Aim 3). Finally, (3) we will explore the macroscopic neuro-vascular relationship between fast and hemodynamic evoked responses (Aim 4). The validation study of the fast signal with concurrent electrophysiology, and EEG/MEG measurements will lead to the investigation of how different phenomena that underlie the electromagnetic and the fast signals correlate temporally, spatially, and in amplitude. The simultaneous and co-localized optical measurement of quantities sensitive to fast (neuronal) and slow (hemodynamic) phenomena will advance our understanding of brain physiology by revealing amplitude/spatial/temporal features of neuro-vascular coupling not currently accessible with existing imaging techniques. The long-term objective of this project is to apply DOI to the study of normal brain development in infants, and to the diagnosis and follow-up of cerebrovascular diseases and psychiatric syndromes in adults and children. [unreadable] [unreadable]